Some viruses require the gene functions of other viruses to replicate. The viruses that rescue such replication-deficient viruses are known as helper viruses. Adenoviruses, herpes simplex virus 1 and 2 (HSV-1, HSV-2) (see Herpesvirus), cytomegalovirus, and pseudorabies virus are helpers for adeno-associated viruses (AAVs), dependoviruses of Parvoviridae family. In addition, hepatitis B virus is a helper virus for hepatitis D virus, and most standard viruses are helpers for their deletion mutants, which are called defective interfering particles. Defective viruses and their helper viruses are usually closely related in many replication processes (see Rous Sarcoma Virus (RSV)). It is now considered, however, that the helper functions are not simple and that they involve the interaction between virus and cells in addition to between defective virus and helper virus.
Genetic analysis of helper functions has been most extensive for adenoviruses. Five regions of the adenovirus genome are required for a permissive AAV infection. They are the E1A, E1B, E2A, E4, and VA regions. The E1A region is required for the trans-activation of the AAV p5 and p19 promoters. The E1B-coded 55-kDa transforming protein and the E4 gene product, a 35-kDa protein, are both required for the efficient accumulation of AAV messenger RNAs. Their role in AAV replication is believed to be to stabilize the AAV mRNAs and assist their transport to the cytoplasm. The E2A gene product, an adenovirus DNA-binding protein, and the adenovirus VA RNAs are required primarily for the efficient translation of AAV mRNA to produce the viral capsid protein.
Although a helper virus is necessary for fully permissive AAV infection, helper virus genes appear not to be directly involved in AAV DNA replication. AAV DNA replication may use primarily cellular factors that exist in cells. The role of helper virus gene products may stimulate the synthesis of cellular genes that are required for AAV DNA replication.
